Murine typhus is unique among the major arthropod-borne infections in that it can be a household infection because of its intimate association with commensal animals and their fleas. Existing knowledge does not adequately explain many important features and mechanisms which are involved in the extraordinarily successful spread, establishment and maintenance of this zoonosis. This research proposal will examine, under controlled conditions in the laboratory, using quantitative techniques, selected components and interactions of the rickettsia-vector complex. The project goals are: (1) To study and define quantitatively the rickettsia vector interrelationships in murine typhus infection, including the course of infection and means of transmission, in three species of fleas. Factors such as rickettsial growth cycle, vector competence, rickettsial virulence and cytopathology will be investigated; (2) To study the reservoir mechanisms for Rickettsia typhi infection, in both fleas and rats. This work will also explore variations in the cellular and organ locations of rickettsiae in both naturally and experimentally infected fleas over a period of several generations. To determine and study the role of the rat as a reservoir of R.typhi, we will test the hypothesis that reactivation of latent rickettsial infection occurs in a presumably immune host long after the original infection, and that rickettsiae reappear in a transmissible form that could infect a new series of vectors. This will be investigated in R.typhi-infected rats at different time points after infection under various stress conditions (e.g. pregnancy and lactation, other parasitic infections); and (3) To study the impact of physiological and environmental changes on R.typhi, as it cycles between the arthropod vector and mammalian host, may undergo changes in antigenic properties and cellular fine structure.